A program to investigate the synthesis and biological activity of the following classes of compounds is proposed: 1) Cytochalasins, 2) pyrrolizidine alkaloids, and 3) aziridine- or oxazole-derived antitumor agents. These projects will require the investigation of nitrogen heterocycles containing 3 to 8 members, and will feature different aspects of the interrelated chemistry of aziridines, oxazoles, pyrroles, pyrrolizidines, and azocines. The cytochalasin project will focus on the completion of the cytochalasin D synthesis, and on the preparation of analogues with potentially selective binding capabilities at cell membrane receptors that mediate transport phenomena. The route has reached the stage of 11-membered carbocycles, and further investigations are directed at specific problems of medium ring functionalization and stereochemistry. The pyrrolizidine project will establish access to macrocyclic dilactones derived from otonecine. The 8-membered nitrogen ring (azocine) of the parent alkaloid is related to the larger class of pyrrolizidine antitumor agents by oxidative ring cleavage, and a sulfur-based route to the azocine system has been developed. The largest effort will be devoted to the synthesis of known and potential aziridine antitumor agents. Our first target will be an aziridinomitosene, the mitomycin metabolite that is responsible for biological activity. The route depends on azomethine ylide generation via oxazolium salt reduction. An important part of this project will be the investigation of direct asymmetric synthesis of aziridines via epimination procedures. Routes to optically pure aziridines will be explored in depth due to their importance in synthesis, and as components of several important classes of antitumor agents. Related techniques for oxazole synthesis will be explored as well.